The present invention relates to a process for preparing N-tert-butoxycarbonylmaleimide from maleimide and di-tert-butyl dicarbonate.
N-tert-Butoxycarbonylmaleimide and copolymers thereof with styrene are reported in the "Abstract of Papers" of the Polymer Society of Korea Fall National Meeting, Oct. 13-14, 1989, pages 56-57. Homo- and copolymers with tert-butoxycarbonylmaleimide units are also disclosed in U.S. Pat. No. 4,775,609 and EP-A 0 234 327. They are prepared from the corresponding polymers without tert-butoxycarbonyl groups. Nothing is disclosed in these publications regarding processes for preparing monomeric tert-butoxycarbonylmaleimide.
tert-Butyl carbamates and their preparation from secondary amines and derivatives of carbonic acid are known. T. W. Greene, Protective Groups in Organic Synthesis, page 232, New York (1981) The introduction of the tert-butoxycarbonyl ("t-BOC") protective group into maleimide has to date involved considerable difficulties. When the reaction was attempted under basic conditions, for example, using an alkali, e.g., potassium carbonate; trialkylamines, e.g., triethylamine or pyridine; metal hydrides, e.g., NaH; alcoholates, e.g., potassium tert-butanolate, or organolithium compounds, e.g., tert-butyllithium, polymerization of the maleimide generally occurred.
The polymerization generally observed in basic media can be prevented by means of a multi-stage procedure. For this purpose, the C-C double bond of the maleimide is first "protected", for example, by a Diels-Alder reaction with cyclopentadienes. The reaction with di-tert-butyl dicarbonate in a basic medium can then take place in a subsequent stage. It is then necessary to introduce the double bond again, for example, by a retro-Diels-Alder reaction. However, such an expensive, multi-stage process is not very useful under practical conditions.
Acidic conditions also proved unsuitable since the t-BOC group is eliminated by acid. In an acidic medium, therefore, in the most favorable case, a dynamic equilibrium is established between the free and the t-BOC-protected amine groups.